Role of dendritic cells and Th2 lymphocytes in asthma: Lessons from eosinophilic airway inflammation in the mouse

Rijt, Leonie S. van; Lambrecht, Bart N.

doi:10.1002/jemt.1092

Cited by 36 publications

(27 citation statements)

References 188 publications

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“…However, it is likely to be related to the inhibitory effect of iIDC on IL-5 production by T cells. IL-5 has been found to play a central role in eosinophil biology, by means of promoting the differentiation and maturation of eosinophil-basophil lineage-committed progenitors [39,40], as well as the circulation, recruitment and survival of mature eosinophils [41]. Recent studies have shown that IL-5 can up-regulate IL-5R § on BM CD34 + progenitors [42].…”

Section: Discussionmentioning

confidence: 99%

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

et al. 2004

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Our previous study has shown that Chlamydia lung infection can inhibit local eosinophilic inflammation induced by allergen sensitization and challenge, which is correlated with altered cytokine production. In the present study, we examined the role played by dendritic cells (DC) in chlamydial infection-mediated modulation of allergic responses. The results showed that DC freshly isolated from Chlamydia-infected mice (iIDC), unlike those from naive control mice (iNDC), could efficiently modulate immune responses to ovalbumin in vitro and in vivo. Co-culture of freshly isolated DC with naive CD4 cells from T cell receptor transgenic mice (DO11.10) showed that iIDC directed Th1-dominant, while iNDC directed Th2-dominant, allergen-specific CD4 T cell responses. Moreover, adoptive transfer of iIDC, but not iNDC, could inhibit systemic and local eosinophilia induced by allergen exposure. The reduction of eosinophilia was associated with a decrease in IL-5 receptor expression on bone marrow cells and the production of IL-5 and IL-13 by T lymphocytes. Analysis of the DC showed that iIDC expressed significantly higher levels of mRNA for Toll-like receptor 9 and produced more IL-12 compared to iNDC. The data demonstrate a critical role played by DC in infection-mediated inhibition of allergic responses.

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Section: Discussionmentioning

confidence: 99%

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

et al. 2004

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“…Since previous studies have shown that PD-L2 expression may be regulated in some cell types by Th2 cytokines or Th2 cells [21], and because asthma is believed to be a Th2-driven disease [23][24][25][26][27][28][29][30][31][32], it was of interest to examine whether PD-L2 can play a role in immune regulation in this context.…”

Section: Discussionmentioning

confidence: 99%

“…Asthma is a chronic disease which can be characterized by airway hyper-responsiveness, mucus hypersecretion by goblet cells, infiltration of the airway wall with leukocytes, and elevation of serum IgE [23 24]. Studies in mouse models have established a critical role for Th2 cells, DC, Treg [24][25][26][27][28], and the Th2 type cytokines IL-4, IL-5, IL-9, and IL-13 in the asthmatic response [23,26,[29][30][31][32]. The role of the PD-1/PD-L1/PD-L2 axis in asthma is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo

et al. 2004

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Programmed death-1 ligand 2 (PD-L2) is a ligand for programmed death-1 (PD-1), a receptor that plays an inhibitory role in T cell activation. Since previous studies have shown upregulation of PD-L2 expression by Th2 cytokines, and asthma is driven by a Th2 response, we hypothesized that PD-L2 might be involved in regulation of the immune response in this disease. We have found that lungs from asthmatic mice had sustained up-regulation of PD-1 and PD-L2, with PD-L2 primarily on dendritic cells. Although addition of PD-L2-Fc in vitro led to decreased T cell proliferation and cytokine production, administration of PD-L2-Fc in vivo in a mouse asthma model resulted in elevated serum IgE levels, increased eosinophilic and lymphocytic infiltration into bronchoalveolar lavage fluid, higher number of cells in the draining lymph nodes, and production of IL-5 and IL-13 from these cells. Although PD-1 was expressed on regulatory T cells, PD-L2-Fc did not affect regulatory T cell activity in vitro. This study provides in vivo evidence of an exacerbated inflammatory response following PD-L2-Fc administration and indicates a potential role for this molecule in Th2-mediated diseases such as asthma.

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“…Furthermore, DC of asthmatics display an enhanced amount of FceRI on their surface in comparison to non-asthmatics (52,53). This process implies a pivotal role of DC in allergen induced immune responses since DC are able to induce a strong pulmonary inflammatory reaction mediated through the activation of T-cells and eosinophils which infiltrate the airways and are responsible for the increased production of the Th2 cytokines IL-4 and IL-5 (54,55) found in the bronchial lavage fluid. They are also responsible for an increased local IgE production within the mucosa by plasma cells.…”

Section: Antigen Presenting Cells Of the Lower Respiratory Tractmentioning

confidence: 99%

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

Novak

Allam

Betten

et al. 2003

Allergy

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It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti‐inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro‐inflammatory reactions and actively induce a T‐cell response, yet on the other hand they serve an important function as ‘silencers’ in the immune system by sending out anti‐inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both – accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.

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Role of dendritic cells and Th2 lymphocytes in asthma: Lessons from eosinophilic airway inflammation in the mouse

Cited by 36 publications

References 188 publications

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

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